Gochujang attenuates colorectal cancer by promoting colonic SCFA utilization and GPCR expression despite limited recovery of microbial diversity

Gut microbiota-derived short-chain fatty acids (SCFAs) and their receptors, G protein-coupled receptors (GPCRs), are essential for maintaining colonic barrier integrity and regulating inflammation, which are markedly impaired in colorectal cancer (CRC). Although Gochujang (GCJ), a Korean traditional fermented food, improves disease-driven gut microbiota imbalance, its potential role in CRC amelioration through modulation of SCFA utilization and GPCR expression has not been explored. In this study, CRC was induced in mice using the AOM/DSS model, followed by oral administration of GCJ (0.6 g/kg). GCJ significantly reduced tumor numbers and improved colon pathology, exhibiting no signs of systemic toxicity. Notably, GCJ did not restore CRC-associated alterations in gut microbiota diversity or increase colonic SCFA levels. Instead, GCJ changed gene expression involved in colonocyte energy metabolism by upregulating SCFA oxidation (e.g., Acss1 and Cpt2 ) and downregulating glycolysis (e.g., c-Myc and Hk-2 ). GCJ also markedly upregulated Gpr41 , Gpr43 , and Gpr109a gene expression, accompanied by enhanced tight junction-related gene expressions and reduced pro-inflammatory gene levels. Correlation analyses demonstrated associations between GPCR expression, barrier integrity, inflammation, and tumor burden. These findings suggest that GCJ may attenuate CRC by enhancing SCFA utilization and GPCR expression, rather than by restoring gut microbial diversity or increasing SCFA production.